DE3884319T2 - Imidazobenzodiazepines and their acid addition salts, processes and intermediates for their preparation, their use as medicaments and preparations containing them. - Google Patents

Abstract

A compound selected from the group consisting a compound of the formula <IMAGE> I wherein R1 is selected from the group consisting of phenyl, cycloalkyl of 4 to 6 carbon atoms and <IMAGE> R4 and R5 are individually hydrogen or alkyl of 1 to 5 carbon atoms, R6 is selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms, phenyl, halogen, alkoxycarbonyl of 2 to 5 carbon atoms, cyano, amido and mono- and dialkylamido of 1 to 5 alkyl carbon atoms, R2 and R3 are individually selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms and cycloalkyl of 3 to 5 carbon atoms or taken together form alkylene of 3 to 5 carbon atoms, X and Y are individually selected form the group consisting of hydrogen, halogen, -NO2, azido, -CN, -CF3 and alkyl and alkoxy of 1 to 3 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts capable of inducing an affinity for benzodiazepine receptors and a novel process and novel intermediates for their preparation.

Description

The invention relates to new imidazobenzodiazepines and their salts, as well as the process and the intermediates for their preparation, the use of these new products as medicines and preparations containing them.

European patent application EP-A-0 027 214 describes imidazo-[1,5-a][1,4]-benzodiazepines substituted in position 3 by a cyano, alkanyl or alkoxycarboxyl group.

The invention relates to new imidazobenzodiazepines of the general formula (I)

wherein R₁ represents a phenyl radical, a cycloalkyl radical having 4 to 6 carbon atoms or a group of the formula (II)

wherein R₄ represents a hydrogen atom or a linear or branched alkyl radical having 1 to 5 carbon atoms, R₅ represents a hydrogen atom or a linear or branched alkyl radical having 1 to 5 carbon atoms, R₆ represents a hydrogen atom, a linear or branched alkyl radical having 1 to 5 carbon atoms, a phenyl radical, a halogen atom, an alkoxycarbonyl radical having 2 to 5 carbon atoms, a cyano group, an amido group, a mono- or dialkylamido radical in which the linear or branched alkyl groups contain 1 to 5 carbon atoms, R₂ and R₃, which are the same or different, stand for a hydrogen atom, a linear or branched alkyl radical having 1 to 5 carbon atoms, a cycloalkyl group having 3 to 5 carbon atoms, or R₂ and R₃ together form an alkylene radical having 3 to 5 carbon atoms, X and Y, which are the same or different, stand for a hydrogen atom, a halogen atom, an alkyl radical or alkoxy radical having 1 to 3 carbon atoms, a nitro group, an azido group, a nitrile group or a trifluoromethyl group, and their addition salts with mineral or organic acids.

In the general formula (I) and in the following,

- cycloalkyl radical with 4 to 6 carbon atoms preferably a cyclobutyl, cyclopentyl or cyclohexyl group;

- alkyl radical with 1 to 5 carbon atoms preferably means a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl or pentyl group;

- halogen atom preferably means a fluorine, chlorine or bromine atom;

- an alkoxycarbonyl radical having 2 to 5 carbon atoms is preferably a methoxycarbonyl, ethoxycarbonyl or propoxycarbonyl group;

- among mono- or dialkylamido radicals whose alkyl radicals contain 1 to 5 carbon atoms, preferably a monomethylamido, dimethylamido, monoethylamido, diethylamido, monopropylamido or dipropylamido group;

- an alkoxy radical having 1 to 3 carbon atoms is preferably a methoxy, ethoxy, propoxy or isopropoxy group.

The addition salts with mineral or organic acids can be, for example, salts formed with hydrogen chloride, hydrogen bromide, hydrogen iodide, Nitric, sulphuric, phosphoric, propionic, formic, benzoic, maleic, fumaric, succinic, tartaric, citric, oxalic, glyoxylic, aspartic acids, alkanesulphonic acids such as methanesulphonic acid and arylsulphonic acids such as benzenesulphonic acid.

Among the compounds according to the invention, mention may be made in particular of the derivatives of the above formula (I) and of their salts, characterized in that in the formula (I) R1 represents a cyclopropyl group and R2, R3, X and Y are as defined above. Among the latter, mention may be made in particular of the derivatives of the above formula (I) and of their salts, characterized in that in the formula (I) R1 represents a cyclopropyl group, R2 and R3, which may be the same or different, represent a hydrogen atom or a methyl group, X and Y, which may be the same or different, represent a hydrogen atom, a fluorine atom or a bromine atom. Among the compounds according to the invention, special mention should be made of the compound with the following name: 3-(5,6-dihydro-5-methyl- 6-oxo-4H-imidazo-[1,5a] [1,4]-benzodiazepinyl)-cyclopropylmethanone.

The invention also relates to a process for the preparation of the new imidazobenzodiazepines of the formula (IA)

wherein R₂, R₃, X and Y are as defined above, and R'₁ represents a phenyl radical, a cycloalkyl radical having 4 to 6 carbon atoms or a group of the formula (II) wherein R₄ represents a hydrogen atom, and R₅ and R₆, which are the same or different, represent a hydrogen atom or an alkyl radical having 1 to 5 carbon atoms, and their salts, characterized in that a compound of the formula (V)

wherein X, Y, R₂ and R₃ are as defined above, with a compound of formula (VI):

wherein Ra is a methyl or methoxy group, or an acid addition salt thereof to give a compound of formula (III)

wherein R₂, R₃, Ra, X and Y are as defined above, then reacting the compound of formula (III) with a compound of formula (IV):

M - R'₁ (IV)

wherein M represents an alkali metal atom such as a lithium atom or a group -Mg-Hal, wherein Hal represents a chlorine, bromine or iodine atom, and R'₁ is as defined above, to obtain the desired compound of formula IA, which is optionally converted into a salt.

In a preferred embodiment of the invention, the above-described method for production is characterized in that

- the reaction of the compound of formula (V) with the compound of formula (VI) is preferably carried out in dimethylformamide;

- the reaction of the compound of formula (III) with the compound of formula (IV) is carried out under anhydrous conditions in an organic solvent such as tetrahydrofuran.

The compounds of formula (V) can be prepared, for example, according to European Patent No. 109921.

The invention also relates to a process for the preparation of the new imidazobenzodiazepines of the above-defined formula IA and their salts, which is characterized in that a compound of the formula (VIII):

wherein X, Y, R₂ and R₃ are as defined above, with a compound of formula (IV) defined above to obtain a compound of formula (VII):

wherein R'₁, R₂, R₃, X and Y are as defined above, then oxidizing the compound of formula (VII) thus obtained to obtain the desired compound of formula (IA), which is optionally converted into a salt.

According to a preferred embodiment of the invention, the above manufacturing process is characterized in that

- the reaction of the compound of formula (VIII) with the compound of formula (IV) is carried out under anhydrous conditions in an organic solvent such as tetrahydrofuran;

- the oxidation of the compound of formula (VII) is preferably carried out with manganese dioxide, nitric acid, iron(III) chloride or chromium oxide in the presence of pyridine or by the Oppenauer process or finally by dehydrogenation in the presence of a copper-based catalyst.

The compounds of formula (VIII) can be prepared, for example, as described in the European patent application published under No. 0027214.

The invention further relates to a process for the preparation of the new imidazobenzodiazepines of the formula (IB):

wherein R₂, R₃, R₄, R₅, X and Y are as defined above and R'₆ represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 5 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, a phenyl group, a cyano group or a group

wherein Rb and R'b, which are the same or different, represent a hydrogen atom or an alkyl radical having 1 to 5 carbon atoms, which is characterized in that

- either a compound of formula (III) as defined above with a compound of formula (X)

wherein M, R₄ and R₅ are as defined above to give a compound of formula (IX):

wherein R₂, R₃, R₄, R₅, X and X are as defined above,

- or reacting a compound of formula (VIII) as defined above with a compound of formula (X) to obtain a compound of formula (XI):

wherein R₂, R₃, R₄, R₅, X and Y are as defined above, then oxidizing the compound of formula (XI) thus obtained with an oxidizing agent to obtain a compound of formula (IX), which is reacted with a suitable cyclizing agent to obtain a compound of formula (IB) as defined above, wherein R'₆ represents a hydrogen atom, a halogen atom, an alkyl radical having 1 to 5 carbon atoms, an alkoxycarbonyl radical having 2 to 5 carbon atoms or a phenyl radical, then optionally saponifying the compound obtained in which R'₆ represents an alkoxycarbonyl radical to obtain a compound of formula (XIII):

wherein R₂, R₃, R₄, R₅, X and Y are as defined above, then reacting this compound of formula (XIII) with an amine of formula (XII):

wherein Rb and R'b are as defined above, to obtain a compound of formula IB' wherein R'6 is a group of formula

then optionally dehydrating the last-mentioned compound, in which Rb and R'b are hydrogen, to obtain a compound corresponding to the formula IB' in which R'6 is cyano, and optionally saponifying the compounds of the formula IB thus obtained.

According to a preferred embodiment of the invention, the manufacturing process described above is characterized in that

- the reaction of the compounds of formulas (III) and (VIII) with the compound of formula (X) is carried out under anhydrous conditions in an organic solvent, such as tetrahydrofuran;

- the oxidation of the compound of formula (XI) is preferably carried out with manganese dioxide, nitric acid, iron(III) chloride or chromium oxide, in the presence of pyridine or furthermore by the Oppenauer process or by dehydrogenation in the presence of a copper-based catalyst;

- the appropriate cyclizing agent is a reagent capable of introducing the group

into the double bond;

- when it is desired to obtain a compound of formula (IB) in which R4 represents an alkyl radical having 1 to 5 carbon atoms, R5 represents a hydrogen atom and R'6 represents a hydrogen atom or an alkyl radical having 1 to 5 carbon atoms, the cyclization is advantageously carried out using trialkyloxosulfonium iodide in an organic solvent such as dimethylformamide;

- when it is desired to obtain a compound of formula (IB)' in which R4 represents a hydrogen atom, R5 represents an alkyl radical having 1 to 5 carbon atoms, and R'6 represents a hydrogen atom or an alkyl radical having 1 to 5 carbon atoms, the cyclization is advantageously carried out with dimethylaminoalkylphenyloxosulfonium tetrafluoroborate in an organic solvent such as dimethylformamide;

- when it is desired to obtain a compound of formula (IB) in which R4 represents a hydrogen atom and R'6 represents an alkoxycarbonyl or phenyl group, the cyclization is advantageously carried out using dimethylsulfuranylidene acetate or using a benzyldimethylsulfonium anion in an organic solvent such as chloroform;

- when it is desired to obtain a compound of formula (IB) in which R4 represents a hydrogen atom and R'6 represents a halogen atom, the cyclization is advantageously carried out with dimethylaminophenyloxosulfonium halomethylylide in an organic solvent such as dimethylformamide;

- the saponification of the compound of formula (IB) in which R6 is an alkoxycarbonyl radical is preferably carried out using an alkali metal hydroxide such as sodium hydroxide;

- the reaction of the compound of formula (IB) with the amine of formula (XII) is preferably carried out in an anhydrous organic solvent in the presence of carbonyldiimidazole;

- the dehydration of the compound of formula (IB) is carried out, preferably with a strong acid anhydride, such as trifluoroacetic anhydride, in an organic solvent, such as dichloromethane.

The compounds of formula (I) have a basic character. The addition salts of the compounds of formula (I) can advantageously be prepared by reacting a mineral or organic acid with the above-mentioned compounds of formula (I) in exactly stoichiometric ratios. The salts can be prepared without isolating the corresponding bases.

The compounds of the invention possess very interesting pharmacological properties, in particular some show weak inverse agonist properties and all have a longer duration of action compared to other, similar imidazobenzodiazepines.

Some compounds exhibit, among other things, tranquilizer properties.

These properties are explained in more detail in the experimental section below.

These properties justify the use of the new imidazobenzodiazepines of formula (I) and their pharmaceutically acceptable salts as medicaments.

The invention also relates to the use of these new imidazobenzodiazepines, as defined by the general formula (I), as well as their addition salts with pharmaceutically acceptable acids, as medicaments.

Among the medicaments according to the invention, particular mention should be made of the medicaments characterized in that they are obtained from the new imidazobenzodiazepines of formula (I) in which R₁ represents a cyclopropyl group, R₂, R₃, X and Y are as defined above, as well as their addition salts with pharmaceutically acceptable acids.

Among the medicaments according to the invention, mention should be made in particular of those of formula (I), characterized in that in formula (I) R₁ represents a cyclopropyl group, R₂ and R₃, which may be identical or different, represent a hydrogen atom or a methyl group, X and Y, which may be identical or different, represent a hydrogen atom or a fluorine or bromine atom, and their addition salts with pharmaceutically acceptable acids.

Among the preferred medicaments of the invention, 3-(5,6-dihydro-5-methyl-6-oxo-4H-imidazo-[1,5a][1,4]-benzodiazepinyl)-cyclopropylmethanone and the pharmaceutically acceptable salts thereof are particularly noteworthy.

These drugs are used, for example, in the treatment of memory disorders, especially in geriatrics, and brain aging disorders. Certain compounds can also be used in the treatment of obesity, as well as minor tranquilizers in the treatment of certain states of restlessness or irritability and in certain forms of epilepsy.

The usual dose, which varies according to the compound used, the patient being treated and the underlying disorder, may be, for example, 0.1 mg to 200 mg daily by the oral route.

The invention also relates to pharmaceutical preparations which comprise at least one of the above derivatives or one of its acid addition salts with pharmaceutically acceptable acids as active ingredient.

As a medicament, the derivatives of formula (I) and their addition salts with pharmaceutically acceptable acids can be incorporated into pharmaceutical preparations to be taken via the digestive route or via the parenteral route.

These pharmaceutical preparations may, for example, be solid or liquid, and they may be in the form currently available in the They may be in pharmaceutical forms used in human medicine, such as plain or coated tablets, gelatin capsules, capsules, granules, suppositories, injection preparations. They are manufactured using conventional processes. The active ingredient(s) may contain excipients commonly used in such pharmaceutical preparations, such as talc, gum arabic, lactose, starch, magnesium stearate, cocoa butter, aqueous or non-aqueous vehicles, fats of animal or vegetable origin, paraffin derivatives, glycols, various plasticizers, dispersants or emulsifiers, preservatives.

Furthermore, as new compounds and in particular as intermediates necessary for the preparation of the compounds of formula (I), the invention relates to:

- The compounds of formula (VII):

wherein R'₁, R₂, R₃, X and Y are as defined above.

- The compounds of formula (XI):

wherein R₂, R₃, R₄, R₅, X and Y are as defined above.

- The compounds of formula (IX):

wherein R₂, R₃, R₄, R₅, X and Y are as defined above.

- The compounds of formula (III):

wherein R₂, R₃, Ra, X and Y are as defined above.

- The compounds of formula (XIII):

wherein R₂, R₃, R₄, R₅, X and Y are as defined above.

Embodiments of the invention are given below.

Example 1: 3-(5,6-Dihydro-5-methyl-6-oxo-4H-imidazo-[1,5-a]- [1,4]-benzodiazepinyl)-cyclopropylmethanone. Step A: 3-(5,6-Dihydro-5-methyl-6-oxo-4H-imidazo-[1,5-a]- [1,4]-benzodiazepinyl)-cyclopropylmethanol

To a solution of 1.82 g of 5,6-dihydro-5-methyl-6-oxo-4H- imidazo-[1,5-a]-[1,4]-benzodiazepine-3-carboxaldehyde in 50 cm3 of tetrahydrofuran is added at ambient temperature 22.7 cm3 of a solution of 0.5 M cyclopropylmagnesium bromide. After 30 min at reflux, another 1.4 cm3 of the magnesium-containing solution is added and the mixture is then stirred for 18 h at ambient temperature. The suspension is poured into 100 cm3 of water and ice, filtered, then the solvent is evaporated and extracted with chloroform. Evaporate to dryness under reduced pressure and chromatograph the residue (2.5 g) on silica gel using chloroform-methanol (96:4) as eluant. 1.47 g of the desired compound are obtained. Mp = 126-128ºC, crystallized from a mixture of ethyl acetate-petroleum ether (m.p. 60-80ºC).

NMR spectrum (CDCl₃) 8.05 (d.d); 7.86 (s); 7.61 (d.t.); 7.49 (d.t); 7.40 (d.d) 4.30-4.68 (br, 2H); 4,19 (d.d); 3.24 (S, MeN); 1.39 (m); 0.68 and 0.50 (2xm, 2x2H).

IR spectrum (KBr) 3360 br; 1640; 1630; 1495; 1395; 1225; 1033; 942; 760 cm-1.

Step B: 3-(5,6-Dihydro-5-methyl-6-oxo-4H-imidazo-[1,5-a]- [1,4]-benzodiazepinyl)-cyclopropylmethanone.

1.87 g of 3-(5,6-dihydro-5-methyl-6-oxo-4H-imidazo-[1,5-a]-[1,4]-benzodiazepinyl)-cyclopropylmethanol in 120 cm³ of methylene chloride are stirred for 1 h with 5.75 g of manganese oxide, a further 5.75 g of manganese oxide are added, the mixture is stirred for 2 h, filtered and evaporated to dryness under reduced pressure. The residue is dried over silica gel with chloroform as eluent. After recrystallization from ethyl acetate, 1.27 g of the desired product with a melting point of 191-193°C are obtained.

NMR spectrum: (CDCl₃) 8.05 (d.d); 7.88 (s); 7.63 (d.t.); 7.53 (d.t); 7.41 (d.d); 5.28 and 4.33 (2xbr, 2H); 3.23 (s, 3H); 3.18 (m); 1.25 (br, 2H) and 1.08 (br, 2H).

IR spectrum: (KBr) 3100; 1735; 1565; 1495; 1390; 1250; 1230; 755 cm-1

Analysis: C₁₆H₁₅N₃O₂

Calculated: C % 68.31; H % 5.37; N % 14.94

Found: 68.38; 5.43; 14.95.

Example 2: (8-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo- [1,5-a]-[1,4]-benzodiazepin-3-yl)-cyclopropylmethanone. Stage A: (8-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo- [1,5-a]-[1,4]benzodiazepin-3-yl-N-methyl-carbohydroxamate (Preparation A).

To a solution of 4.26 g of 8-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-[1,5-a]-[1,4]-benzodiazepine-3-carboxylic acid in 70 cm3 of dimethylformamide is added 7.12 g of 1,1-carbonyldiimidazole, stirred at 50°C for 3 h, cooled to 0°C and centrifuged. 3.79 g of imidazolyl intermediate are obtained, which is stirred at 60°C with 75 cm3 of dimethylformamide and 3.25 g of dimethylhydroxylamine chlorohydrate. After 1 h 30 min, cool and pour into 300 cm3 of water. Extract with ethyl acetate and concentrate under reduced pressure. 3.15 g of the desired compound are obtained.

Step B: (8-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo- [1,5-a]-[1,4]-benzodiazepin-3-yl)-cyclopropylmethanone.

20 cm³ of a cyclopropylmagnesium bromide solution in tetrahydrofuran is mixed with a solution of the product obtained in step A. compound in 20 cm3 of tetrahydrofuran. After stirring for 1 hour and 30 minutes at room temperature, the medium is decomposed in an ammonium chloride solution and extracted with chloroform. It is dried, evaporated under reduced pressure and the residue is chromatographed on silica gel using methylene chloride-ethyl acetate as eluent. 704 mg of the desired compound are obtained, crystallized from ethyl acetate with a melting point of 230-232ºC.

The following N-methylcarbohydroxamate derivatives were prepared in an identical manner to Step A.

Preparation B

(5,6-Dihydro-5-methyl-6-oxo-4H-imidazo-[1,5-a][1,4]- benzodiazepin-3-yl)-N-methylcarbohydroxamate.

Preparation C

(5,6-Dihydro-8-fluoro-5-methyl-6-oxo-4H-imidazo-[1,5-a][1,4]-benzodiazepin-3-yl)-N-methylcarbohydroxamate.

Preparation D

(8-Bromo-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-[1,5-a][1,4]-benzodiazepin-3-yl)-N-methylcarbohydroxamate.

The following cyclopropylmethanone derivatives were prepared as in Example 2.

Example 3:

(5,5-Dihydro-8-fluoro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]-benzodiazepin-3-yl)-cyclopropylmethanone.

Example 4:

(8-Bromo-5,6-dihydro-5-methyl-6-oxo-4H-imidazo- [1,5-a]-[1,4]-benzodiazepin-3-yl)-cyclopropylmethanol.

The following phenylmethanone derivatives were prepared as in Example 2 using phenylmagnesium bromide instead of cyclopropylmagnesium bromide.

Example 5:

(5,6-Dihydro-5-methyl-6-oxo-4H-imidazo-[1,5- a][1,4]-benzodiazepin-3-yl)-phenylmethanone.

Example 6:

(5,6-Dihydro-8-fluoro-5-methyl-6-oxo-4H-imidazo- [1,5-a][1,4]-benzodiazepin-3-yl)-phenylmethanone.

Example 7:

(8-Chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo- [1,5-a][1,4]-benzodiazepin-3-yl)-phenylmethanone.

Example 8:

(8-Bromo-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-[1,5-a]-[1,4]-benzodiazepin-3-yl)-phenylmethanone. Example or Preparation Yield Formula Calculated Found aromatic A= -aldehyde B= -hydroxamate C= -imidazole

Example 9:

Tablets are manufactured according to the following formulation:

- Compound according to Example 1 20 mg

- Excipient q.s.q for one tablet of 150 mg

(Composition of the excipient: Lactose, starch, talc, magnesium stearate).

Pharmacological action

The compounds of the invention are agents which show interaction with the benzodiazepine receptors in the brain, some of which may be useful for treating obesity or cognitive disorders, and some of which may be useful as mild tranquilizers. Screening for binding to the benzodiazepine receptors (BRB) was carried out according to the method described in patent GB 2128989.

a) The ability of the compounds to induce contractions of the tongue muscle of rats was investigated according to the method of V.W. James and C.R. Gardner (Eur. J. Pharmacol (1985), 113, 233).

b) Enhancement of convulsions induced by subcutaneous leptazole injection in CD1 mice.

A dose of leptazole is chosen which produces 10 to 20% convulsions in untreated CD1 mice. The drugs increase the percentage of convulsions and the ED50 is calculated according to the method of Lichfield and Wilcoxon (J. Pharmacol. Exp. Ther. (1949) 96, 99). Compound Tongue muscle contraction (mg/kg) Leptazole cramps ED₅₀ (mg/kg) not effective

Claims (15)

1) New imidazobenzodiazepines of the general formula (I): wherein R₁ represents a phenyl radical, a cycloalkyl radical having 4 to 6 carbon atoms or a group of the formula (II): wherein R₄ represents a hydrogen atom or a linear or branched alkyl radical having 1 to 5 carbon atoms, R₅ represents a hydrogen atom or a linear or branched alkyl radical having 1 to 5 carbon atoms, R₆ represents a hydrogen atom, a linear or branched alkyl radical having 1 to 5 carbon atoms, a phenyl radical, a halogen atom, an alkoxycarbonyl radical having 2 to 5 carbon atoms, a cyano group, an amido group, a mono- or dialkylamido group whose linear or branched alkyl groups comprise 1 to 5 carbon atoms, R₂ and R₃, which are the same or different, represent a hydrogen atom, a linear or branched alkyl radical having 1 to 5 carbon atoms, a cycloalkyl radical having 3 to 5 carbon atoms, or R₂ and R₃ together form an alkylene radical having 3 to 5 carbon atoms, X and Y, which are the same or different, represent a hydrogen atom, a halogen atom, an alkyl or alkoxy radical having 1 to 3 carbon atoms, a nitro, azido, nitrile or trifluoromethyl group, as well as their addition salts with mineral or organic acids. 2) New imidazobenzodiazepines of formula (I) according to claim 1, characterized in that in formula (I) R₁ is a cyclopropyl group and R₂, R₃, X and Y are as defined above, as well as their addition salts with mineral or organic acids. 3) New imidazobenzodiazepines of formula (I) according to claim 1 or 2, characterized in that in formula (I) R₁ represents a cyclopropyl group, R₂ and R₃, which are the same or different, represent a hydrogen atom, a methyl group, X and Y, which are the same or different, represent a hydrogen atom, a fluorine or bromine atom, and their addition salts with mineral or organic acids. 4) 3-(5,6-Dihydro-5-methyl-6-oxo-4H-imidazo [1,5a][1,4]benzodiazepinyl)cyclopropylmethanone. 5) Process for the preparation of the new imidazobenzodiazepines of the general formula (IA) according to claim 1 wherein R₂, R₃, X and Y are as defined above, and R'₁ represents a phenyl radical, a cycloalkyl radical having 4 to 6 carbon atoms or a group of the formula (II) wherein R₄ represents a hydrogen atom, and R₅ and R₆ are the same or different are a hydrogen atom or an alkyl radical having 1 to 5 carbon atoms, and their salts, characterized in that -- either a compound of formula (V) wherein X, Y, R₂ and R₃ are as defined above, with a compound of formula (VI): wherein Ra is a methyl or methoxy group, or an acid addition salt to give a compound of formula (III): wherein R₂, R₃, Ra, X and Y are as defined above, then the compound of formula III with a compound the formula (IV): M-R'₁ (IV), wherein M represents an alkali metal atom such as a lithium atom or a -Mg-Hal group wherein Hal represents a chlorine, bromine or iodine atom, and R'₁ are as defined above, to obtain the desired compound of formula (IA) to obtain, which can optionally be converted into a salt, -- or a compound of formula (VIII): wherein X, Y, R₂ and R₃ are as defined above, with a compound of formula (IV) defined above to obtain a compound of formula (VII): wherein R'₁, R₂, R₃, X and Y are as defined above, then oxidizing the compound of formula (VII) thus obtained to obtain the desired compound of formula (IA) which can optionally be converted into a salt. 6) Method for production according to claim 5, characterized in that -- the reaction of the compound of formula (V) with the compound of formula (VI) is preferably carried out in dimethylformamide ; -- the reaction of the compound of formula (III) or (VIII) with the compound of formula (IV) is carried out under anhydrous conditions in an organic solvent such as tetrahydrofuran; -- the oxidation of the compound of formula (VII) is preferably carried out with manganese dioxide, nitric acid, iron(III) chloride or chromium oxide in the presence of pyridine or by the Oppenauer process or finally by dehydrogenation in the presence of a copper-based catalyst. 7) Process for the preparation of the new imidazobenzodiazepines of formula (I) according to claim 1, of general formula (IB): wherein R₂, R₃, R₄, R₅, X and Y are as defined above, and R'₆ represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 5 carbon atoms or an alkoxycarbonyl group having 2 to 5 carbon atoms, a phenyl group, a cyano group or a group wherein Rb and R'b are the same or different and represent a hydrogen atom or an alkyl radical having 1 to 5 carbon atoms, characterized in that -- either a compound of formula (III) as defined above with a compound of formula (X): wherein M, R₄ and R₅ are as defined above to give a compound of formula (IX): to obtain, wherein R₂, R₃, R₄, R₅, X and Y are as defined above, -- or reacting a compound of formula (VIII) as defined above with a compound of formula (X) to obtain a compound of formula (XI): wherein R₂, R₃, R₄, R₅, X and Y are as defined above, then oxidizing the compound of formula (XI) thus obtained with an oxidizing agent to obtain a compound of formula (IX), which can be reacted with a suitable cyclizing agent to obtain a compound of the formula (IB) defined above, in which R'₆ represents a hydrogen atom, a halogen atom, an alkyl radical having 1 to 5 carbon atoms, an alkoxycarbonyl radical having 2 to 5 carbon atoms or a phenyl radical, then optionally saponifying the compound obtained, in which R'₆ represents an alkoxycarbonyl radical, to obtain a compound of the formula wherein R₂, R₃, R₄, R₅, X and Y are as defined above, then reacting the compound of formula (XIII) with an amine of formula (XII): wherein Rb and R'b are as defined above, to obtain the compound of formula (IB) wherein R'6 is a group of formula then optionally dehydrating the last-mentioned compound, in which Rb and R'b are hydrogen, to obtain a compound of formula IB' in which R'6 is cyano, and optionally converting the compounds of formula IB thus obtained into a salt. 8) Process for the preparation according to claim 7, characterized in that the reaction of the compounds of formulas (III) and (VIII) with the compound of formula (X) is carried out under anhydrous conditions in an organic solvent such as tetrahydrofuran. 9) Process for the preparation according to claim 7, characterized in that the oxidation of the compound of formula (XI) is preferably carried out with manganese dioxide, nitric acid, iron (III) chloride or chromium oxide in the presence of pyridine, or also according to the Oppenauer process or also by dehydrogenation in the presence of a copper-based catalyst. 10) Method for production according to claim 7, characterized in that - the appropriate cyclizing agent is a reagent with the ability to introduce the -group in the double bond; - when a compound of formula (IB) in which R4 is an alkyl radical having 1 to 5 carbon atoms, R5 is a hydrogen atom and R'6 is a hydrogen atom or an alkyl radical having 1 to 5 carbon atoms is to be obtained, the cyclization is preferably carried out using trialkyloxosulfonium iodide in an organic solvent such as dimethylformamide; - when a compound of formula (IB) in which R4 is a hydrogen atom, R5 is an alkyl radical having 1 to 5 carbon atoms and R'6 is a hydrogen atom or an alkyl radical having 1 to 5 carbon atoms is to be obtained, the cyclization is preferably carried out using dimethylaminoalkylphenyloxosulfonium tetrafluoroborate in an organic solvent such as dimethylformamide; - if a compound of formula (IB) in which R₄ is a hydrogen atom and R'₆ is an alkoxycarbonyl or phenyl radical is to be obtained, the cyclization preferably carried out using dimethylsulfuranylidene acetate or the benzyldimethylsulfonium anion in an organic solvent such as chloroform; - when a compound of formula (IB) in which R4 represents a hydrogen atom and R'6 represents a halogen atom is to be obtained, the cyclization is preferably carried out using dimethylaminophenyloxosulfonium halomethylylide in an organic solvent such as dimethylformamide; 11) Method for production according to claim 7, characterized in that - the saponification of the compound of formula (IB) in which R'6 represents an alkoxycarbonyl radical is preferably carried out using an alkali hydroxide such as sodium hydroxide; - the reaction of the compound of formula (IB) with the amine of formula (XII) is preferably carried out in an anhydrous organic solvent in the presence of carbonyldiimidazole; - the dehydration of the compound of formula (IB) is preferably carried out with a strong acid anhydride, such as trifluoroacetic anhydride, in an organic solvent, such as dichloromethane. 12) Medicaments, characterized in that they contain the new imidazobenzodiazepines of the formula (I) according to claim 1, as well as their pharmaceutically acceptable salts. 13) Medicaments, characterized in that they contain the new imidazobenzodiazepines according to one of claims 2, 3 or 4, and their pharmaceutically acceptable salts. 14) Pharmaceutical preparations, characterized in that they contain as active ingredient at least one of the medicaments according to one of claims 12 or 13. 15) As new industrially usable products: - The compounds of formula (VII): wherein R'₁, R₂, R₃, X and Y are as defined above; - The compounds of formula (XI): wherein R₂, R₃, R₄, R₅, X and Y are as defined above; - The compounds of formula (IX): wherein R₂, R₃, R₄, R�5 are as defined above; - The compounds of formula (III): wherein R₂, R₃, Ra, X and Y are as defined above; -The compounds of formula (XIII): wherein R₂, R₃, R₄, R�5, X and Y are as defined above